Initial studies with primarily vascularized murine cardiac allografts which are implanted by microsurgical anastomosis have revealed prolonged survival of B10.BR, but rejection of B10.D2, hearts in B6AF1 recipients. The animals are probably not classically tolerant, and rejection of long-term grafts can be induced. The hypothesis that suppressor cells mediate the long-term graft acceptance will be investigated in this grant. Lymphocytes from the recipients will be evaluated for their capacity to suppress the following donor-specific immune responses: mixed lymphocyte culture (MLC) reactions, the MLC generation of lymphocyte mediated cytotoxicity (LMC), donor skin graft survival on the recipient strain, induction of specific delayed cutaneous hypersensitivity, and sensitization for protection against tumor growth. Then, using these assays, the temporal relationship to graft rejection of any suppressor cell activity which may be demonstrated will be studied. The effect on a parabiont animal of removal from a long-term graft-carrying partner will be evaluated. The effect on graft survival of low-dose immunosuppression, which may inhibit suppressor cell activity will be studied. Anti-donor immune reactivity of the long-term recipients will be studied by several immunologic tests including the Winn Assay of tumor graft rejection. The capacity of recipient cells to specifically reconstitute tolerant mice will be tested. Finally, other congenic strain pairs will be similarly evaluated, to place in perspective the relevance of the above results to the immunology of graft rejection.